Adherence to Dutch Guideline in Hospitalized Anorexia Nervosa Adolescents.

Background. The Dutch guideline Eating Disorders defines admission criteria for children with anorexia nervosa (AN) in need for medical stabilization and advices close monitoring to detect refeeding syndrome (RFS) in an early stage. Methods. Admission criteria, recommendations at admission, and during first week of hospitalization were evaluated in accordance to the guideline. RFS was defined as decreased electrolyte concentrations and/or clinical features. Results. 22 patients were included with a total of 50 admissions. We observed that 62% of the admitted patients met one of the admission criteria, 190/300 (63%) recommended admission examinations were performed. During admission adherence decreased, in particular daily weighing and physical examination (12% and 6%, respectively). The guideline was not fully followed in any of the patients. None of the hospitalized patients met the RFS criteria. Conclusion. Guideline adherence was moderate and can be improved by a few adaptations, which may limit unnecessary laboratory testing.

[Not to be missed signs of primary amenorrhea]. / Niet te missen signalen van primaire amenorroe.

Primary amenorrhea is defined as the absence of the menarche by the age of 16. Knowledge of the new arrangement of all causes into four pathofysiologic compartments by the NVOG and NVK guideline contributed the diagnostic process. This article present the alarm symptoms of primary amenorrhea in the anamnesis, physical examination and supplementary tests including the interpretation of stages of puberty in relation with length and vaginal examination. In this article, we propose the optimal diagnostic traject for general practitioner, pediatrician and gynaecologist. We describe four cases, one of each compartment, to illustrate the importance of this process.

Comparison of Centers for Disease Control and Prevention and World Health Organization references/standards for height in contemporary Australian children: analyses of the Raine Study and Australian National Children's Nutrition and Physical Activity cohorts.

AIM: (i) To compare the Centers for Disease Control and Prevention (CDC) reference and World Health Organization (WHO) standard/reference for height, particularly with respect to short stature and eligibility for growth hormone (GH) treatment by applying them to contemporary Australian children; (ii) To examine the implications for identifying short stature and eligibility for GH treatment. METHODS: Children from the longitudinal Raine Study were serially measured for height from 1991 to 2005 (2-15-year-old girls (660) and boys (702) from Western Australia). In the cross-sectional Australian National Children's Nutrition and Physical Activity survey (2-16-year-old boys (2415) and girls (2379) from all states), height was measured in 2007. Heights were converted to standard deviation scores (SDSs) based on CDC and WHO. RESULTS: Means and standard deviations of height-SDS varied between CDC and WHO definitions and with age and gender within each definition. However, both identified similar frequencies of short stature (<1st centile for GH eligibility), although these were very significantly less than the anticipated 1% (0.1-0.7%) of the Australian cohorts. Mean heights in the Australian cohorts were greater than both the WHO and CDC means. CONCLUSIONS: Neither CDC nor WHO height standardisations accurately reflect the contemporary Australian child population. Australian children are taller than the CDC or WHO height means, and significantly less than 1% of Australian children are defined as being short using either CDC or WHO. This study suggests there may be a case for an Australian-specific standard/reference for height.

Long-term follow-up of GH-treated girls with Turner syndrome: BMI, blood pressure, body proportions.

AIMS: To investigate whether long-term growth hormone (GH) treatment influenced blood pressure (BP), body proportions and BMI in young Turner syndrome (TS) women several years after GH discontinuation. METHODS: A follow-up study of a randomized GH dose-response trial with 3 GH dosages (1.3, 2.0, and 2.7 mg/m(2)/day). 39 TS patients (20.0 +/- 2.1 years) participated 4.8 (1.9) years after GH discontinuation. Mean GH duration was 8.7 (2.0) years. MEASUREMENTS: BP, BMI and body proportions. RESULTS: During GH treatment, DBP had decreased. At the long-term follow-up study, DBP had increased and was similar to pretreatment levels. DBP was negatively influenced by GH dose. SBP was not influenced by GH dose or duration. The BMI increased gradually during and after GH therapy. During GH therapy, shape values of sitting height had decreased to normal values, of foot had increased, and both remained constant after GH discontinuation. CONCLUSIONS: GH therapy in girls with TS has, besides height, additional beneficial effects on BP and body proportions, except foot length. Nearly 5 years after ending GH, the favorable effect of GH on BP was still noticeable. The BMI increased gradually over the years, not influenced by GH.

Long-term follow-up of GH-treated girls with Turner syndrome: metabolic consequences.

AIMS: To investigate the metabolic consequences of long-term GH treatment in young women with Turner syndrome (TS), several years after GH discontinuation. METHODS: Follow-up study of a randomized GH dose-response trial, with 3 GH dosages (1.3, 2.0, and 2.7 mg/m(2)/day). Thirty-nine TS patients (20.0 +/- 2.1 years) participated 4.8 +/- 1.9 years after GH discontinuation. Mean GH treatment duration was 8.7 +/- 2.0 years. Fasting glucose, insulin, and serum lipids were measured. RESULTS: Several years after GH discontinuation, insulin sensitivity remained lower, while beta-cell function and fasting insulin levels remained higher than before treatment. Only BMI influenced beta-cell function. Serum total cholesterol (TC), low-density lipoprotein and high-density lipoprotein (HDL) had further increased compared to 6 months after GH, resulting in higher TC, but also higher HDL levels compared to controls. The atherogenic index remained constant, but lower than controls. CONCLUSIONS: Besides height, GH therapy in girls with TS has additional beneficial effects on serum lipids. Nearly 5 years after discontinuation of GH therapy the favorable effect of GH was still noticeable. The GH-induced decrease in insulin sensitivity, however, remained unchanged, possibly due to having TS.

Cardiac status after childhood growth hormone treatment of Turner syndrome.

CONTEXT: In Turner syndrome (TS), GH treatment is well established. Data on cardiac status after discontinuation of treatment are scarce. This study aimed to assess biventricular size and function in TS at least 6 months after discontinuation of GH treatment. METHODS: TS patients and healthy women prospectively underwent cardiac magnetic resonance imaging. Ventricular two-dimensional tomographic cine data were acquired to obtain biventricular volume, mass, and ejection fraction. Atrioventricular valve flow measurements were performed using a two-dimensional flow-sensitized sequence. Flow velocity curves were calculated and indices of biventricular diastolic filling were derived. RESULTS: Thirty-one patients [mean (sd) age 20 (2) yr, body surface area 1.75 (0.15) m(2), 5 (2) yr after GH discontinuation] and 23 normal control women [age 21 (2) yr, body surface area 1.80 (0.13) m(2)] were included. Compared with controls, patients had smaller mean end-diastolic volumes [right ventricle (RV), 84 (11) ml/m(2) vs. 79 (10), P = 0.02; left ventricle (LV), 81 (10) vs. 72 (9), P < 0.001], end-systolic volumes [RV 38 (7) ml/m(2) vs. 36 (6), P = 0.04; LV 34 (5) vs. 29 (4), P < 0.001], and stroke volumes [RV 46 (6) ml/m(2) vs. 43 (6), P = 0.03; LV, 47 (7) vs. 44 (4), P = 0.02]. Patients had a higher mean heart rate [79 (13) beats/min vs. 71 (10), P < 0.05]. Biventricular ejection fraction, mass, cardiac output, and diastolic filling pattern were comparable. CONCLUSION: After discontinuation of GH treatment TS patients showed no myocardial hypertrophy and well-preserved biventricular function. Ventricular volumes were smaller in Turner patients, compared with controls, whereas mean heart rate was higher. These last observations may be part of the natural development in TS and not linked to GH treatment, which at this point we consider safe.

Subclassification of small for gestational age children with persistent short stature: growth patterns and response to GH treatment.

AIM: We determined whether subclassification of short small for gestational age (SGA) children according to birth anthropometrics could delineate different patterns in gestation, delivery, postnatal growth, response to growth hormone (GH) treatment and parental height. METHODS: 201 short SGA children were divided into three groups, SGA(L), SGA(L+W) and SGA(L+W+HC), according to birth length (L), weight (W) and head circumference (HC) < or =-2.00 standard deviation score (SDS). RESULTS: SGA(L+W+HC) children were born after the shortest gestational age and more often by caesarean section than SGA(L) children (36.3 vs. 38.1 weeks, 68.4 vs. 24.4%). SGA(L+W) children had an intermediate pattern and experienced most gestational hypertension (p = 0.01). At birth, SGA(L+W+HC) children were shorter than SGA(L) or SGA(L+W) (-4.12 vs. -2.67 and -3.72 SDS, p < or = 0.001). During the first 3 years of life, SGA(L+W+HC) children exhibited an increased growth in height (0.98 SDS) and HC (1.28 SDS) than SGA(L) (height, -0.06 SDS; HC, -0.30 SDS) and SGA(L+W) (height, 0.62 SDS; HC, -0.31 SDS). However, HC SDS remained smaller for SGA(L+W+HC) than the other groups at age 3. The groups did not differ in growth response during GH treatment. SGA(L) children tended to have shorter parents and target height than SGA(L+W+HC) children. CONCLUSIONS: Our study shows that subclassification of short SGA children might be a useful method for investigating SGA children as the subgroups revealed a different gestation, delivery and postnatal growth pattern. Response to GH treatment was not different between the groups.

Free/dissociable insulin-like growth factor (IGF)-I, not total IGF-I, correlates with growth response during growth hormone treatment in children born small for gestational age.

CONTEXT: IGF-I plays an important role in pre- and postnatal growth. Its serum levels are regulated by metabolic and genetic factors. Mean total IGF-I in short, small for gestational age (SGA) children is reduced, but within the normal range. Free/dissociable IGF-I is the bioactive form of IGF-I. OBJECTIVES: The aim of the study was to investigate changes in free IGF-I during GH treatment in short SGA children and to evaluate whether free IGF-I levels contribute to predicting first-year growth response and/or adult height. DESIGN, SETTING, AND INTERVENTION: We conducted a randomized, double-blind GH dose-response study with a GH dose of either 1 mg/m(2).d (group A) or 2 mg/m(2).d (group B). Free IGF-I, total IGF-I, and IGF binding protein (IGFBP)-3 were determined at baseline, after 1 and 5 yr, at stop, and 6 months after GH discontinuation. PATIENTS: We studied 73 (46 male) short SGA children (36 group A) with a baseline mean age of 7.7 (2.2) yr and a mean GH duration of 8.2 (2.1) yr. MAIN OUTCOME MEASURES: Untreated SGA children had a mean free IGF-I sd score (SDS) of -0.2 (1.2), not related to total IGF-I. During GH therapy, free IGF-I significantly increased to 1.6 (0.7) SDS, as did total IGF-I and IGFBP-3 [2.0 (0.8) and 1.3 (0.9), respectively]. Multiple regression analysis showed that baseline free IGF-I and IGFBP-3 were negatively correlated with adult height SDS, whereas baseline bone age delay, target height SDS, baseline height SDS, and GH dose were positively correlated. Free IGF-I was also negatively correlated with first-year growth response. CONCLUSIONS: Circulating baseline free IGF-I and IGFBP-3 were better predictors for adult height in GH-treated SGA children than total IGF-I, or total IGF-I to IGFBP-3 ratio. This suggests a possible role for free IGF-I measurement in predicting the effect of GH therapy in short SGA children.

Risk factors for diabetes mellitus type 2 and metabolic syndrome are comparable for previously growth hormone-treated young adults born small for gestational age (sga) and untreated short SGA controls.

CONTEXT: Low birth weight might increase risk of diabetes mellitus type 2 and metabolic syndrome (MS). GH has insulin-antagonistic properties. Therefore, long-term follow-up of GH-treated children born small for gestational age (SGA) is important. OBJECTIVE AND PATIENTS: The objective of the study was to evaluate insulin sensitivity (Si) and disposition index (DI), all components of the MS and IGF-I and IGF binding protein (IGFBP)-3 levels in 37 previously GH-treated young SGA adults in comparison with 25 untreated short SGA controls. RESULTS: GH-treated subjects were 22.3 (1.7) yr old. Mean duration of GH treatment had been 7.3 (1.3) yr. Mean period after discontinuation was 6.5 (1.4) yr. Si and DI were comparable for GH-treated and untreated SGA subjects. Fasting glucose and insulin levels increased during GH treatment but recovered after discontinuation. Body mass index, waist circumference, high-density lipoprotein cholesterol levels, and triglycerides were equivalent. Systolic and diastolic blood pressure and cholesterol were significantly lower in GH-treated subjects. Thirty-two percent of untreated controls vs. none of the GH-treated subjects had an increased blood pressure. GH-induced rises in IGF-I and IGFBP-3 levels had completely recovered after GH stop. CONCLUSION: At 6.5 yr after discontinuation of long-term GH treatment, Si, DI, fasting levels of glucose and insulin, body mass index, waist circumference, and IGF-I and IGFBP-3 levels were equivalent for GH-treated and untreated young SGA adults. Systolic and diastolic blood pressure and serum cholesterol were even lower in GH-treated subjects. These data are reassuring because they suggest that long-term GH treatment does not increase the risk for diabetes mellitus type 2 and MS in young adults.

Free dissociable insulin-like growth factor I (IGF-I), total IGF-I and their binding proteins in girls with Turner syndrome during long-term growth hormone treatment.

OBJECTIVE: To investigate the effect of GH treatment on free IGF-I levels in girls with Turner syndrome (TS) and to verify relationships between free IGF-I levels and total IGF-I, IGFBP-1, 2 and 3. Additionally, to analyse whether free IGF-I, total IGF-I, IGFBP-3 or its ratio were related to IGF-I bioactivity outcome parameters. DESIGN: Sixty-five girls with TS were randomly assigned to three different GH-dosage groups (1.3, 2.0 and 2.7 mg/m2/day). Mean duration of GH therapy was mean (SD) 8.7(2.0) years. Free IGF-I, total IGF-I and IGFBP-1, -2, -3 were determined at baseline, first, second, third and fifth year of GH therapy, before the start of oestrogen therapy, during the final year of GH treatment, 6 months after GH and 4.8(2.0) years after GH discontinuation. MAIN OUTCOME: During GH treatment, mean free IGF-I levels stayed < +2 standard deviation score (sds), whereas mean total IGF-I and IGF-I/IGFBP-3 ratio were > +2 sds. There were no differences in free IGF-I levels between the three GH groups, whereas total IGF-I and ratio levels were significantly higher in the highest GH group. The following variables contributed significantly to predicting the square root of free IGF-I levels: age, GH dose, oestrogen dose, IGFBP-1, IGFBP-3, body mass index and total IGF-I or IGF-I/IGFBP-3 ratio. However, the explaining variance did not exceed 55%. Several IGF-I bioactivity outcome parameters positively correlated with total IGF-I and IGF-I/IGFBP-3 ratio, whereas free IGF-I did not. CONCLUSIONS: During long-term GH therapy in girls with TS, mean free IGF-I levels stayed within the normal range, whereas mean total IGF-I and IGF-I/IGFBP-3 ratio exceeded the upper normal range. Although total IGF-I and the IGF-I/IGFBP-3 ratio did not accurately represent free IGF-I levels, they seemed to better represent the IGF-I bioactivity than the measured free IGF-I.

Aortic distensibility and dimensions and the effects of growth hormone treatment in the turner syndrome.

In Turner's syndrome (TS), an increased risk for cardiovascular malformations exists, including aortic dilation of unknown cause. Abnormal biophysical wall properties may play an important role. Magnetic resonance imaging has been successfully used to assess aortic size and wall distensibility. The aim of this study was to assess aortic biophysical properties and dimensions in TS. Thirty-eight former participants of a growth hormone (GH) dose-response study in TS (mean age 12 +/- 2 years, mean body surface area 1.7 +/- 0.2 m2) and 27 controls (mean age 21 +/- 2 years, mean body surface area 1.8 +/- 0.1 m2) were enrolled. Previously, patients had been assigned to 1 of 3 groups treated with different GH dosages: group A (0.045 mg/kg/day), group B (0.067 mg/kg/day), and group C (0.09 mg/kg/day). All underwent magnetic resonance imaging > or =6 months after GH discontinuation to determine aortic dimensions and distensibility at 4 predefined levels: (1) the ascending aorta, (2) the descending aorta, (3) the level of the diaphragm, and (4) the abdominal aorta. Patients had larger aortic diameters at all but level 4 and tended to have reduced distensibility at level 3. Distensibility in group A was significantly less compared with that in group C at level 4. Compared with controls, patients in group A had larger aortic diameters at all but level 4 and reduced distensibility at level 4. The results for patients in groups B and C were not different from those for controls. In conclusion, patients with TS formerly treated with GH have dilated aortas and signs of impaired wall distensibility. The severity of abnormalities seems related to the GH dose, with a beneficial effect of a larger GH dose on the abnormalities.

Quality of life after growth hormone therapy and induced puberty in women with Turner syndrome.

OBJECTIVE: To evaluate health-related quality of life (HRQoL) in young women with Turner syndrome (TS) after long-term growth hormone (GH) therapy and induced puberty and to analyze whether HRQoL was influenced by auxologic parameters, pubertal development, or subjective parameters. STUDY DESIGN: The study group comprised 49 women with TS, mean (standard deviation) age 19.6 (+/-3.0) years, all former participants of 2 GH studies, > or =6 months after GH discontinuation. Puberty was induced by estrogen treatment, at mean age 12.9 (+/-1.1) years. HRQoL was measured by self-reports of the 2 generic questionnaires, SF36 and TAAQOL. As an additional source of information on HRQoL, we applied parental proxy reports. RESULTS: HRQoL of the women with TS was normal. Remarkably, the women with TS had higher HRQoL scores on some of the scales, including "social functioning" and "role-emotional." Satisfaction with height and breast development had a positive influence on several HRQoL scales. CONCLUSIONS: The young women with TS who reached normal height and had age-appropriate pubertal development reported normal HRQoL. The relatively high scores on some of the HRQoL scales can be explained by an estrogen effect or by a possible response shift, indicating a different internal reference in women with TS. We hypothesize that GH and estrogen treatment positively influenced HRQoL in young women with TS.

Quality of life in adolescents born small for gestational age: does growth hormone make a difference?

BACKGROUND/AIMS: To evaluate quality of life (QoL) in adolescents born SGA without spontaneous catch-up growth, treated with and without long-term growth hormone (GH) therapy. Additionally, to assess whether GH treatment has a positive effect on QoL, besides improving adult height and height SDS during childhood. METHODS: Two groups of adolescents born SGA without spontaneous catch-up growth participated in the QoL evaluation; a GH-treated group (n = 44, mean GH duration: 8.8 (1.7) years) and an untreated group (n = 28), both mean age 15.8 (2.1) years. QoL was measured by self-reports of the TACQOL-S, a disorder-specific questionnaire, and the CHQ, a generic questionnaire. RESULTS: The GH group scored significantly better health status and health-related QoL on several scales of the TACQOL-S. On all TACQOL-S scales the GH group scored better QoL than the untreated group, with effect sizes of moderate to large, not all differences reaching statistical significance. The generic CHQ did not reveal significant differences in QoL between the GH group and the untreated group. CONCLUSIONS: Firstly, adolescents born SGA, with a GH-induced improved height, had in many aspects a better QoL than untreated adolescents born SGA, according to the disorder-specific questionnaire. Secondly, we advise to use, in addition to a generic questionnaire, a disorder-specific questionnaire for measuring QoL in children treated for short stature, as the generic CHQ did not reveal such differences.